PMID- 17634255
OWN - NLM
STAT- MEDLINE
DCOM- 20070913
LR  - 20230216
IS  - 0022-3166 (Print)
IS  - 0022-3166 (Linking)
VI  - 137
IP  - 8
DP  - 2007 Aug
TI  - Rapamycin limits formation of active eukaryotic initiation factor 4F complex 
      following meal feeding in rat hearts.
PG  - 1857-62
AB  - Feeding promotes protein synthesis in cardiac muscle through a stimulation of the 
      messenger RNA translation initiation phase of protein synthesis by enhancing 
      assembly of active eukaryotic initiation factor (eIF)4F complex. The experiments 
      reported herein examined the potential role for a rapamycin-sensitive signaling 
      pathway in increasing formation of active eIF4G-eIF4E complex during meal 
      feeding. Hearts from male Sprague-Dawley rats fed a meal consisting of rat 
      nonpurified diet were sampled prior to and 3 h following the meal in the presence 
      or absence of treatment with rapamycin, an inhibitor of the mammalian target of 
      rapamycin (mTOR) complex 1. Rapamycin prevented the meal feeding-induced 
      stimulation of myocardial protein synthesis. Inhibition of mTOR with rapamycin 
      decreased the association of rapamycin-associated TOR protein with mTOR and 
      prevented the feeding-induced assembly of eIF4G-eIF4E complex. In contrast, the 
      abundance of eIF4E binding protein-1 (4E-BP1)-eIF4E complex was unaffected by 
      either meal feeding or rapamycin. Pretreatment with rapamycin completely 
      prevented the feeding-induced phosphorylation of eIF4G(Ser(1108)), whereas the 
      inhibitor only partially attenuated meal feeding-induced 70-kDa ribosomal protein 
      S6 kinase1(Thr(389)) phosphorylation and extent of 4E-BP1 in the gamma-form. Meal 
      feeding-induced phosphorylation of protein kinase B on either Ser(473) or 
      Thr(308) was unaffected by rapamycin. These findings suggest the extent of 
      phosphorylation of eIF4G following meal feeding occurs by a rapamycin-sensitive 
      mechanism in cardiac muscle. Furthermore, the rapamycin-sensitive reductions in 
      phosphorylation of eIF4G may also lead to decreased formation of active 
      eIF4G-eIF4E complex.
FAU - Vary, Thomas C
AU  - Vary TC
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State University 
      College of Medicine, Hershey, PA 17033, USA. tvary@psu.edu
FAU - Deiter, Gina
AU  - Deiter G
FAU - Lynch, Christopher J
AU  - Lynch CJ
LA  - eng
GR  - AA-12814/AA/NIAAA NIH HHS/United States
GR  - DK-062880/DK/NIDDK NIH HHS/United States
GR  - R01 DK062880-05A1/DK/NIDDK NIH HHS/United States
GR  - R01 DK062880/DK/NIDDK NIH HHS/United States
GR  - R01 DK062880-07/DK/NIDDK NIH HHS/United States
GR  - GM-39722/GM/NIGMS NIH HHS/United States
GR  - DK-053843/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 0 (Eukaryotic Initiation Factor-4F)
RN  - 0 (Eukaryotic Initiation Factor-4G)
RN  - 0 (Multiprotein Complexes)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases
MH  - Animal Nutritional Physiological Phenomena
MH  - Animals
MH  - Eukaryotic Initiation Factor-4F/chemistry/*metabolism
MH  - Eukaryotic Initiation Factor-4G/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Heart/*drug effects
MH  - Male
MH  - Multiprotein Complexes/chemistry/metabolism
MH  - Myocardium/*metabolism
MH  - Phosphorylation
MH  - Postprandial Period
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
EDAT- 2007/07/20 09:00
MHDA- 2007/09/14 09:00
CRDT- 2007/07/20 09:00
PHST- 2007/07/20 09:00 [pubmed]
PHST- 2007/09/14 09:00 [medline]
PHST- 2007/07/20 09:00 [entrez]
AID - S0022-3166(22)09327-0 [pii]
AID - 10.1093/jn/137.8.1857 [doi]
PST - ppublish
SO  - J Nutr. 2007 Aug;137(8):1857-62. doi: 10.1093/jn/137.8.1857.